Is ACADVL p.Phe262Ser (c.785T>C) pathogenic?

ACADVL p.Phe262Ser (c.785T>C) is classified Uncertain significance in ACADVL (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-07-15). AlphaMissense: likely pathogenic (0.9947); Very rare (popmax 0.000508%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ACADVL p.Phe262Ser (c.785T>C)?

ACADVL p.Phe262Ser (c.785T>C) is associated with Inborn genetic diseases, very long chain acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADVL p.Phe262Ser (c.785T>C) in the general population?

ACADVL p.Phe262Ser (c.785T>C) is very rare (popmax 0.000508%, nfe) (gnomAD).

What do computational predictors say about ACADVL p.Phe262Ser (c.785T>C)?

AlphaMissense predicts likely pathogenic (score 0.9947) — an in-silico prediction, not a clinical call.

ACADVL p.Phe262Ser

c.785T>C · rs1597528061 · VCV811126

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.9947 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9947	likely pathogenic · top 2% in ACADVL
REVEL	0.903	moderately pathogenic-leaning
SaProt	LLR -12.03	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 0.94, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 5,109 bp · p 0.51 · regional, not allelic
Overall
CADD	29.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000508% European (non-Finnish) · 6/1,180,022 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.00041% 6/1,461,846 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ACADVL
Protein: p.Phe262Ser
Coding: c.785T>C
MANE Select: NM_000018
dbSNP: rs1597528061
Type: single nucleotide variant
Location: chr17:7222209 (GRCh38)
Gene constraint: LOEUF 1.077 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.65 · 3 PDB
Residue 262: a β-strand; the 'catalytic' region

Full ACADVL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: very long chain acyl-CoA dehydrogenase deficiency

Similar variants

ACADVL p.Phe262Leu Uncertain significance ★ ⚠ same residue
ACADVL p.Phe262= Likely benign ★ same residue
ACADVL c.1077+1G>A Likely pathogenic ★★★ same condition
ACADVL c.1077+1G>T Likely pathogenic ★★★ same condition
ACADVL c.1077+2T>A Pathogenic ★★★ same condition
ACADVL c.1077+2T>C Pathogenic ★★★ same condition
ACADVL c.1182+1G>A Likely pathogenic ★★★ same condition
ACADVL c.1269+1G>A Likely pathogenic ★★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/acadvl-p-phe262ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown